DBS-STN&SNr combined stimulation versus DBS-STN monotarget stimulation for Parkinson's disease freezing: A comparative efficacy study

Background Freezing of gait (FOG) is a common and disabling symptom in patients with Parkinson's disease (PD), significantly impairing motor function and quality of life. While traditional deep brain stimulation (DBS) of the subthalamic nucleus (STN) provides some benefits, its efficacy in alleviating FOG remains limited. Combined stimulation of the STN and the substantia nigra pars reticulata (SNr) has recently emerged as a potentially superior approach. Objective To compare the efficacy of STN-only stimulation and combined STN + SNr stimulation in improving FOG symptoms and quality of life in patients with PD. Methods This multicenter, prospective, randomized, crossover study was conducted between May 2020 and May 2024 and enrolled patients with PD and significant FOG. All participants received bilateral DBS electrode implantation. Each subject sequentially underwent both STN-only and combined STN + SNr stimulation conditions according to a randomized crossover schedule, with each stimulation period lasting for six months. Outcome assessments, including the Freezing of Gait Questionnaire (FOG-Q) and the Parkinson's Disease Questionnaire Summary Index (PDQ-SI), were conducted at baseline, 6, 12, and 18 months. Data were analyzed using mixed-model repeated-measures analysis of variance, followed by post hoc Bonferroni-adjusted pairwise comparisons to account for the crossover design. Results Compared to STN-only stimulation, combined STN + SNr stimulation resulted in significantly greater improvement in FOG-Q scores and PDQ-SI scores. The benefits were observed at each assessment following the switch to combined stimulation. Conclusions Combined STN and SNr stimulation was more effective than STN-only stimulation in alleviating FOG symptoms and improving quality of life in patients with PD. This dual-target DBS approach may represent a promising therapeutic strategy for managing refractory FOG in PD.